Utilisation Trend of Long-Acting Insulin Analogues including Biosimilars across Europe: Findings and Implications.

BACKGROUND: Diabetes mellitus rates and associated costs continue to rise across Europe enhancing health authority focus on its management. The risk of complications is enhanced by poor glycaemic control, with long-acting insulin analogues developed to reduce hypoglycaemia and improve patient convenience. There are concerns though with their considerably higher costs, but moderated by reductions in complications and associated costs. Biosimilars can help further reduce costs. However, to date, price reductions for biosimilar insulin glargine appear limited. In addition, the originator company has switched promotional efforts to more concentrated patented formulations to reduce the impact of biosimilars. There are also concerns with different devices between the manufacturers. As a result, there is a need to assess current utilisation rates for insulins, especially long-acting insulin analogues and biosimilars, and the rationale for patterns seen, among multiple European countries to provide future direction. Methodology. Health authority databases are examined to assess utilisation and expenditure patterns for insulins, including biosimilar insulin glargine. Explanations for patterns seen were provided by senior-level personnel. RESULTS: Typically increasing use of long-acting insulin analogues across Europe including both Western and Central and Eastern European countries reflects perceived patient benefits despite higher prices. However, activities by the originator company to switch patients to more concentrated insulin glargine coupled with lowering prices towards biosimilars have limited biosimilar uptake, with biosimilars not currently launched in a minority of European countries. A number of activities were identified to address this. Enhancing the attractiveness of the biosimilar insulin market is essential to encourage other biosimilar manufacturers to enter the market as more long-acting insulin analogues lose their patents to benefit all key stakeholder groups. CONCLUSIONS: There are concerns with the availability and use of insulin glargine biosimilars among European countries despite lower costs. This can be addressed.

Potential approaches for the pricing of cancer medicines across Europe to enhance the sustainability of healthcare systems and the implications.

Introduction: There are growing concerns among European health authorities regarding increasing prices for new cancer medicines, prices not necessarily linked to health gain and the implications for the sustainability of their healthcare systems.Areas covered: Narrative discussion principally among payers and their advisers regarding potential approaches to the pricing of new cancer medicines.Expert opinion: A number of potential pricing approaches are discussed including minimum effectiveness levels for new cancer medicines, managed entry agreements, multicriteria decision analyses (MCDAs), differential/tiered pricing, fair pricing models, amortization models as well as de-linkage models. We are likely to see a growth in alternative pricing deliberations in view of ongoing challenges. These include the considerable number of new oncology medicines in development including new gene therapies, new oncology medicines being launched with uncertainty regarding their value, and continued high prices coupled with the extent of confidential discounts for reimbursement. However, balanced against the need for new cancer medicines. This will lead to greater scrutiny over the prices of patent oncology medicines as more standard medicines lose their patent, calls for greater transparency as well as new models including amortization models. We will be monitoring these developments.

Comparison of psychotropic medication use in the Baltic countries.

Purpose: While the pivotal role of pharmacotherapy in psychiatry is universal, significant regional differences exist in drug use patterns. Herewith we compare the use of ATC psychotropic drugs (N05, psycholeptics and N06A, antidepressants) in 2010-2015 in the three Baltic Countries with reference to the Nordic Countries.Methods: Data were obtained from the national authorities on medicines as expressed in DDD per 1000 inhabitants per day. A semi-structured questionnaire was used for expert statements on the rationale of current use of medicines.Results: During the observation period the use of antipsychotics, anxiolytics, hypnotics and sedatives, and antidepressants steadily increased, while the growth in use of anxiolytics stagnated in the more recent years. Antipsychotic use was the largest in Lithuania and the lowest in Estonia. The use on anxiolytics in Lithuania was more than twice of that in Estonia and Latvia. Conversely, the use of hypnotics and sedatives was about three times higher in Estonia than in Latvia or Lithuania. Antidepressant use was dominated by the selective serotonin reuptake inhibitors in all three countries, but overall was much lower in Latvia as compared to Lithuania and Estonia. As compared to the Nordic Countries in 2015, antidepressants are used at much lower level throughout Baltics, probably reflecting underdiagnostics of depression and anxiety disorders.Conclusion: While the health-care expenditures in Estonia, Latvia and Lithuania are largely similar, as is the cultural and recent political background of these EU member countries, the extent and the pattern of psychotropic drug use is remarkably variable.

The Expiry of Humira® Market Exclusivity and the Entry of Adalimumab Biosimilars in Europe: An Overview of Pricing and National Policy Measures.

Background: From October 2018, adalimumab biosimilars could enter the European market. However, in some countries, such as Netherlands, high discounts reported for the originator product may have influenced biosimilar entry. Objectives: The aim of this paper is to provide a European overview of (list) prices of originator adalimumab, before and after loss of exclusivity; to report changes in the reimbursement status of adalimumab products; and discuss relevant policy measures. Methods: Experts in European countries received a survey consisting of three parts: 1) general financing/co-payment of medicines, 2) reimbursement status and prices of originator adalimumab, and availability of biosimilars, and 3) policy measures related to the use of adalimumab. Results: In May 2019, adalimumab biosimilars were available in 24 of the 30 countries surveyed. Following introduction of adalimumab biosimilars, a number of countries have made changes in relation to the reimbursement status of adalimumab products. Originator adalimumab list prices varied between countries by a factor of 2.8 before and 4.1 after loss of exclusivity. Overall, list prices of originator adalimumab decreased after loss of exclusivity, although for 13 countries list prices were unchanged. When reported, discounts/rebates on originator adalimumab after loss of exclusivity ranged from 0% to approximately 26% (Romania), 60% (Poland), 80% (Denmark, Italy, Norway), and 80-90% (Netherlands), leading to actual prices per pen or syringe between €412 (Finland) and €50 - €99 (Netherlands). To leverage competition following entry of biosimilar adalimumab, only a few countries adopted measures specifically for adalimumab in addition to general policies regarding biosimilars. In some countries, a strategy was implemented even before loss of exclusivity (Denmark, Scotland), while others did not report specific measures. Conclusion: Even though originator adalimumab is the highest selling product in the world, few countries have implemented specific policies and practices for (biosimilar) adalimumab. Countries with biosimilars on the market seem to have competition lowering list or actual prices. Reported discounts varied widely between countries.

Proposal for a regulation on health technology assessment in Europe - opinions of policy makers, payers and academics from the field of HTA.

INTRODUCTION: In January 2018 the European Commission published a Proposal for a Regulation on Health Technology Assessment (HTA): 'Proposal for a Regulation on health technology assessment and amending Directive 2011/24/EU'. A number of stakeholders, including some Member States, welcomed this initiative as it was considered to improve collaboration, reduce duplication and improve efficiency. There were however a number of concerns including its legal basis, the establishment of a single managing authority, the preservation of national jurisdiction over HTA decision-making and the voluntary/mandatory uptake of joint assessments by Member States. Areas covered: This paper presents the consolidated views and considerations on the original Proposal as set by the European Commission of a number of policy makers, payers, experts from pricing and reimbursement authorities and academics from across Europe. Expert commentary: The Proposal has since been extensively discussed at Council and while good progress has been achieved, there are still divergent positions. The European Parliament gave a number of recommendations for amendments. If the Proposal is approved, it is important that a balanced, improved outcome is achieved for all stakeholders. If not approved, the extensive contribution and progress attained should be sustained and preserved, and the best alternative solutions found.

Barriers for Access to New Medicines: Searching for the Balance Between Rising Costs and Limited Budgets.

Introduction: There is continued unmet medical need for new medicines across countries especially for cancer, immunological diseases, and orphan diseases. However, there are growing challenges with funding new medicines at ever increasing prices along with funding increased medicine volumes with the growth in both infectious diseases and non-communicable diseases across countries. This has resulted in the development of new models to better manage the entry of new medicines, new financial models being postulated to finance new medicines as well as strategies to improve prescribing efficiency. However, more needs to be done. Consequently, the primary aim of this paper is to consider potential ways to optimize the use of new medicines balancing rising costs with increasing budgetary pressures to stimulate debate especially from a payer perspective. Methods: A narrative review of pharmaceutical policies and implications, as well as possible developments, based on key publications and initiatives known to the co-authors principally from a health authority perspective. Results: A number of initiatives and approaches have been identified including new models to better manage the entry of new medicines based on three pillars (pre-, peri-, and post-launch activities). Within this, we see the growing role of horizon scanning activities starting up to 36 months before launch, managed entry agreements and post launch follow-up. It is also likely there will be greater scrutiny over the effectiveness and value of new cancer medicines given ever increasing prices. This could include establishing minimum effectiveness targets for premium pricing along with re-evaluating prices as more medicines for cancer lose their patent. There will also be a greater involvement of patients especially with orphan diseases. New initiatives could include a greater role of multicriteria decision analysis, as well as looking at the potential for de-linking research and development from commercial activities to enhance affordability. Conclusion: There are a number of ongoing activities across countries to try and fund new valued medicines whilst attaining or maintaining universal healthcare. Such activities will grow with increasing resource pressures and continued unmet need.

Use of a national database as a tool to identify primary medication non-adherence: The Estonian ePrescription system.

BACKGROUND: Medication adherence can be divided into primary and secondary adherence. Primary medication non-adherence (PMN) occurs when a patient does not obtain medicine with their initial prescription. Secondary non-adherence measures prescription refills among patients who previously filled their first prescription. While secondary non-adherence has been studied thoroughly, PMN has been assessed less extensively, due to lack of available data. Estonian ePrescription system might prove a valuable tool for this. OBJECTIVES: The aim of this study was to evaluate PMN and the interval between prescribing and dispensing of medicines using the Estonian ePrescriptions database to establish its potential use for this purpose and for other qualitative drug utilization research measures. Osteoporosis medicines were used as an example. METHODS: The Estonian Prescription Centre was used to evaluate if patients purchase medicines after initial prescription of osteoporosis medicine. Prescriptions from 2012 to 2015 of all patients over 18 were included. PMN was defined as the first prescription not being dispensed before it expired (60 days). The rate of PMN was calculated. RESULTS: Estonian ePrescription System enabled fast evaluation of PMN of osteoporosis patients based on data about prescribing, dispensing and time intervals in-between. Of patients who started osteoporosis treatment 13.1% were primary non-adherent. Of primary non-adherent patients 42% still started treatment at some point during the study. Of patients who did purchase their first prescription 80.4% did so within a week and 95% within 25 days. CONCLUSION: The Estonian ePrescription system is a useful tool for monitoring PMN. The PMN of osteoporosis medicines was identified as lower than previously reported. More similar type of studies about other groups of medicines would be needed to understand the pattern of PMN and give valuable information to healthcare specialists about how to increase initiation of treatment.

Policies for biosimilar uptake in Europe: An overview.

BACKGROUND: Across European countries, differences exist in biosimilar policies, leading to variations in uptake of biosimilars and divergences in savings all over Europe. OBJECTIVES: The aim of this article is to provide an overview of different initiatives and policies that may influence the uptake of biosimilars in different European countries. Recommendations will be formulated on how to create sustainable uptake. METHODS: An overview of policies on biosimilars was obtained via a questionnaire, supplemented with relevant articles. Topics were organized in five themes: availability, pricing, reimbursement, demand-side policies, and recommendations to enhance uptake. RESULTS: In all countries studied, biological medicines are available. Restrictions are mainly dependent on local organization of the healthcare system. Countries are willing to include biosimilars for reimbursement, but for commercial reasons they are not always marketed. In two thirds of countries, originator and biosimilar products may be subjected to internal reference pricing systems. Few countries have implemented specific incentives targeting physicians. Several countries are implementing pharmacist substitution; however, the scope and rules governing such substitution tend to vary between these countries. Reported educational policies tend to target primarily physicians, whereas fewer initiatives were reported for patients. Recommendations as proposed by the different country experts ranged from the need for information and communication on biosimilars to competitive pricing, more support for switching and guidance on substitution. CONCLUSIONS: Most countries have put in place specific supply-side policies for promoting access to biosimilars. To supplement these measures, we propose that investments should be made to clearly communicate on biosimilars and educate stakeholders. Especially physicians need to be informed on the entry and use of biosimilars in order to create trust. When physicians are well-informed on the treatment options, further incentives should be offered to prescribe biosimilars. Gainsharing can be used as an incentive to prescribe, dispense or use biosimilars. This approach, in combination with binding quota, may support a sustainable biosimilar market.

Adaptive Pathways: Possible Next Steps for Payers in Preparation for Their Potential Implementation.

Medicines receiving a conditional marketing authorization through Medicines Adaptive Pathways to Patients (MAPPs) will be a challenge for payers. The "introduction" of MAPPs is already seen by the European Medicines Agency (EMA) as a fait accompli, with payers not consulted or involved. However, once medicines are approved through MAPPs, they will be evaluated for funding by payers through different activities. These include Health Technology Assessment (HTA) with often immature clinical data and high uncertainty, financial considerations, and negotiations through different types of agreements, which can require monitoring post launch. Payers have experience with new medicines approved through conditional approval, and the fact that MAPPs present additional challenges is a concern from their perspective. There may be some activities where payers can collaborate. The final decisions on whether to reimburse a new medicine via MAPPs will have more variation than for medicines licensed via conventional processes. This is due not only to increasing uncertainty associated with medicines authorized through MAPPs but also differences in legal frameworks between member states. Moreover, if the financial and side-effect burden from the period of conditional approval until granting full marketing authorization is shifted to the post-authorization phase, payers may have to bear such burdens. Collection of robust data during routine clinical use is challenging along with high prices for new medicines during data collection. This paper presents the concept of MAPPs and possible challenges. Concerns and potential ways forward are discussed and a number of recommendations are presented from the perspective of payers.

Adherence to osteoporosis medicines in Estonia-a comprehensive 15-year retrospective prescriptions database study.

Some patients do not take medicines as they are supposed to. Our research showed that in Estonia, one fifth of patients did not start treatment with osteoporosis medicines and only 20% used the medicines for at least 3 years as they should. This induces unnecessary costs to the healthcare system. PURPOSE: Medication non-adherence is the number one reason for not obtaining the expected clinical effect of medicines. With osteoporosis treatment, it has been shown that both implementation of treatment and persistence influence the risk of fractures significantly. Long-term adherence to medication in Estonia is to be determined with this study. METHODS: A 15-year retrospective study was carried out in order to establish initiation, implementation, and persistence of Estonian patients. All new users of osteoporosis medicines were analyzed for all prescriptions they received during the study period. Sufficient adherence to treatment was defined as a patient being dispensed 80% or more prescribed doses for at least 1 year. RESULTS: The study period was from 2001 to 2015. Patients (24,652) were included in the study. Of the patients, 93.7% (n = 23,091) were women and 6.3% (n = 1564) were men. Eighteen percent (4636) were dispensed only one prescription. Of the patients, 44.2% included in the study had medication possession ratio (MPR) ≥80% over follow-up period; 8922 (36.2%) who were prescribed from 2001 to 2015 persisted for 1 year with MPR ≥80% and 19.8% persisted for 3 years. Forty percent of expenditure on osteoporosis medication was made for treatment courses with insufficient adherence. CONCLUSIONS: There is room for improvement in Estonia with medication adherence relating to all three aspects that determine adherence-initiation, implementation, and persistence. This means further efforts are to be made to educate patients and healthcare professionals on realizing the importance of good adherence.

Trends in and relation between hip fracture incidence and osteoporosis medication utilization and prices in Estonia in 2004-2015.

Osteoporosis medicines reduce osteoporotic fractures. There is a very strong negative correlation between the consumption of medicines and the price of an average daily dose indicating that affordability is a key factor that could increase consumption of antiosteoporotic medicines and, through that, reduce fractures. PURPOSE: Osteoporosis is a major cause of morbidity and mortality in the modern world. Our study aims to describe the trends in incidence of hip fractures in relation to drug utilization patterns and the average price of antiosteoporotic medicines in Estonia. METHODS: Data on hip fractures was obtained from the medical claims database of Estonian Health Insurance Fund (EHIF). Consumption and price data was obtained from the Estonian State Agency of Medicines (SAM).Consumption is presented using WHO defined daily doses methodology, and the prices reflect the average wholesale price of medicines. RESULTS: From 2004 to 2010 there was a non-significant increasing trend in standardized hip fracture incidence in Estonia, but from 2010 to 2015, the trend turned to a significant decrease of 4.5% per year. The consumption of osteoporosis medication increased significantly from 2004 to 2009 by yearly average of 41.2%. After 2009, the consumption levelled. On contrast, the average price of one daily dose of osteoporosis medication decreased significantly from 2004 to 2009 by 16.9% per year and the decrease also levelled after 2009. This gives a very strong negative correlation of -0.93 (p < 0.001) between the consumption of antiosteoporotic medication and the average price of a daily dose of medication during the study period. CONCLUSIONS: The statistically significant decline of standardized incidence of hip fractures from 2010 onward could at least in part be the result of the high increase in consumption of antiosteoporotic medicines which in turn is strongly negatively correlated with the average price of osteoporosis medicines.

Comparing policies to enhance prescribing efficiency in Europe through increasing generic utilization: changes seen and global implications.

AIM: The aim of this article was to evaluate the influence of different demand-side measures to enhance the prescribing of generics in ambulatory care based on cross-national comparisons. METHODS: An observational retrospective study was conducted using administrative databases from across Europe, documenting changes in reimbursed utilization and expenditure of different proton pump inhibitors (PPIs) and statins between 2001 and 2007, alongside different reforms to enhance prescribing efficiency. Utilization was converted to defined daily doses (DDDs) and expenditures were converted to euros. Demand-side measures were collated under the '4 Es'--education, engineering, economics and enforcement--to enable comparisons on the nature and intensity of reforms between countries. RESULTS: There were considerable differences in the utilization of generics and patent-protected PPIs and statins among Western European countries. Decreased utilization of omeprazole and simvastatin, alongside increased utilization of esomeprazole, atorvastatin and rosuvastatin, was seen in countries with limited demand-side measures to counteract commercial pressures. Prescribing restrictions, or a combination of education, prescribing targets and financial incentives, had the greatest influence on enhancing the utilization of omeprazole and simvastatin. For example, there was a threefold reduction in the utilization of atorvastatin in Austria following prescribing restrictions. Multiple demand-side interventions generally had a greater influence than single interventions, with the impact appearing additive. Multiple interventions coupled with initiatives to lower prices of generics considerably enhanced prescribing efficiency. CONCLUSION: This cross-national study has demonstrated considerable variation in the utilization and expenditure of PPIs and statins across Europe, providing opportunities to further improve prescribing efficiency. The '4 Es' do provide an understandable methodology to document and compare the influence of different demand-side measures, with the influence varying by their extent and intensity. Further reforms are essential given current financial pressures. Consequently, further research will concentrate on the potential to develop a scoring system to help predict the possible impact of different demand-side measures on future utilization patterns.

Risk sharing arrangements for pharmaceuticals: potential considerations and recommendations for European payers.

BACKGROUND: There has been an increase in 'risk sharing' schemes for pharmaceuticals between healthcare institutions and pharmaceutical companies in Europe in recent years as an additional approach to provide continued comprehensive and equitable healthcare. There is though confusion surrounding the terminology as well as concerns with existing schemes. METHODS: A literature review was undertaken to identify existing schemes supplemented with additional internal documents or web-based references known to the authors. This was combined with the extensive knowledge of health authority personnel from 14 different countries and locations involved with these schemes. RESULTS AND DISCUSSION: A large number of 'risk sharing' schemes with pharmaceuticals are in existence incorporating both financial-based models and performance-based/outcomes-based models. In view of this, a new logical definition is proposed. This is "risk sharing' schemes should be considered as agreements concluded by payers and pharmaceutical companies to diminish the impact on payers' budgets for new and existing schemes brought about by uncertainty and/or the need to work within finite budgets". There are a number of concerns with existing schemes. These include potentially high administration costs, lack of transparency, conflicts of interest, and whether health authorities will end up funding an appreciable proportion of a new drug's development costs. In addition, there is a paucity of published evaluations of existing schemes with pharmaceuticals. CONCLUSION: We believe there are only a limited number of situations where 'risk sharing' schemes should be considered as well as factors that should be considered by payers in advance of implementation. This includes their objective, appropriateness, the availability of competent staff to fully evaluate proposed schemes as well as access to IT support. This also includes whether systematic evaluations have been built into proposed schemes.

Use of Generics-A Critical Cost Containment Measure for All Healthcare Professionals in Europe?

Pharmaceutical expenditures in ambulatory care rose rapidly in Europe in the 1990s and early 2000s. This was typically faster than other components of healthcare spending, leading to reforms to moderate future growth. A number of these centered on generic medicines with measures to lower reimbursed prices as well as enhance their prescribing and dispensing. The principal objective of this paper is to review additional measures that some European countries can adopt to further reduce reimbursed prices for generics. Secondly, potential approaches to address concerns with generics when they arise to maximize savings. Measures to enhance the prescribing of generics will also briefly be discussed. A narrative review of the extensive number of publications and associated references from the co-authors was conducted supplemented with known internal or web-based articles. In addition, health authority and health insurance databases, principally from 2001 to 2007, were analyzed to assess the impact of the various measures on price reductions for generic omeprazole and generic simvastatin vs. pre-patent loss prices, as well as overall efficiency in Proton Pump Inhibitor (PPI) and statin prescribing. The various initiatives generally resulted in considerable lowering of the prices of generics as well as specifically for generic omeprazole and generic simvastatin vs. pre-patent loss prices. At one stage in the UK, generic simvastatin was just 2% of the originator price. These measures also led to increased efficiency for PPI and statin prescribing with reimbursed expenditure for the PPIs and statins either falling or increasing at appreciably lower rates than increases in utilization. A number of strategies have also been introduced to address patient and physician concerns with generics to maximize savings. In conclusion, whilst recent reforms have been successful, European countries must continue learning from each other to fund increased volumes and new innovative drugs as resource pressures grow. Policies regarding generics and their subsequent impact on reimbursement and utilization of single sourced products will continue to play a key role to release valuable resources. However, there must continue to be strategies to address concerns with generics when they exist.